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Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats.

Erdely A, Antonini JM, Young SH, Kashon ML, Gu JK, Hulderman T, Salmen R, Meighan T, Roberts JR, Zeidler-Erdely PC - Part Fibre Toxicol (2014)

Bottom Line: In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy.Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS.The effects were not related to transcription, but were observed in conjunction with oxidative stress.

View Article: PubMed Central - HTML - PubMed

Affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown 26505, WV, USA. efi4@cdc.gov.

ABSTRACT
Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically. Our aim was to evaluate the circulating leukocyte population in terms of cellular activation, presence of oxidative stress, and functionality after a secondary challenge, following welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing TruCulture technology. In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Welding fume exposure had rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. These findings support previous studies of an inadequate pulmonary immune response following a metal-rich exposure and extend those findings showing leukocyte dysfunction occurs systemically.

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Effect of MMA-SS welding fume instillation on relative mRNA expression in circulating leukocytes. The Venn diagram represents genes altered due to MMA-SS welding fume exposure, only 16 genes overlapped between 4 and 24 h. The Table indicates the major functional categories altered and the number of genes in each.
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Figure 3: Effect of MMA-SS welding fume instillation on relative mRNA expression in circulating leukocytes. The Venn diagram represents genes altered due to MMA-SS welding fume exposure, only 16 genes overlapped between 4 and 24 h. The Table indicates the major functional categories altered and the number of genes in each.

Mentions: Gene expression analysis showed significant changes at 4 h with 298 network eligible genes. At 24 h after ITI a 75% reduction in the number of eligible genes (74 in total) was found and only 5% of the genes (16 in total) altered at 4 h showed overlap (Figure 3). This indicated a rapidly evolving but controlled response. Cell-to-cell signaling and interaction, inflammatory response, immune cell trafficking, cellular movement, and hematological system development and function were the primary groups derived from the functional analysis (Figure 3). Interestingly, there was little difference in the functional categories despite the minimal overlap of similar genes further illustrating the rapid but controlled response (Figure 3).


Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats.

Erdely A, Antonini JM, Young SH, Kashon ML, Gu JK, Hulderman T, Salmen R, Meighan T, Roberts JR, Zeidler-Erdely PC - Part Fibre Toxicol (2014)

Effect of MMA-SS welding fume instillation on relative mRNA expression in circulating leukocytes. The Venn diagram represents genes altered due to MMA-SS welding fume exposure, only 16 genes overlapped between 4 and 24 h. The Table indicates the major functional categories altered and the number of genes in each.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4151022&req=5

Figure 3: Effect of MMA-SS welding fume instillation on relative mRNA expression in circulating leukocytes. The Venn diagram represents genes altered due to MMA-SS welding fume exposure, only 16 genes overlapped between 4 and 24 h. The Table indicates the major functional categories altered and the number of genes in each.
Mentions: Gene expression analysis showed significant changes at 4 h with 298 network eligible genes. At 24 h after ITI a 75% reduction in the number of eligible genes (74 in total) was found and only 5% of the genes (16 in total) altered at 4 h showed overlap (Figure 3). This indicated a rapidly evolving but controlled response. Cell-to-cell signaling and interaction, inflammatory response, immune cell trafficking, cellular movement, and hematological system development and function were the primary groups derived from the functional analysis (Figure 3). Interestingly, there was little difference in the functional categories despite the minimal overlap of similar genes further illustrating the rapid but controlled response (Figure 3).

Bottom Line: In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy.Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS.The effects were not related to transcription, but were observed in conjunction with oxidative stress.

View Article: PubMed Central - HTML - PubMed

Affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown 26505, WV, USA. efi4@cdc.gov.

ABSTRACT
Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically. Our aim was to evaluate the circulating leukocyte population in terms of cellular activation, presence of oxidative stress, and functionality after a secondary challenge, following welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing TruCulture technology. In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Welding fume exposure had rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. These findings support previous studies of an inadequate pulmonary immune response following a metal-rich exposure and extend those findings showing leukocyte dysfunction occurs systemically.

Show MeSH
Related in: MedlinePlus